Preoperative prescription opioid use as an independent predictor of 90-day mortality and adverse events in craniotomy and craniectomy patients.

OBJECTIVE: A growing body of literature suggests that preoperative opioid exposure is an independent predictor of poor outcomes in surgical patients. No outcomes data exist on preoperative opioid use and craniotomies/craniectomies. The objective of this study was to determine the impact of preoperative opioid use on 90-day adverse events after craniotomy or craniectomy. METHODS: A single-center retrospective cohort study of 2445 patients undergoing a craniotomy/craniectomy between January 1, 2013, and October 1, 2018, was conducted. Baseline demographics, pre- and postoperative opioid use (morphine milligram equivalents [MMEs]), and surgical metrics were recorded. Patients were categorized based on whether they took prescription opioids preoperatively, defined as within 1 month of surgery, or were opioid naive. The outcomes were mortality and adverse events 90 days after craniotomy/craniectomy. RESULTS: Overall, 26.6% of patients composed the preoperative opioid group. The median daily MME intake among this group was 34.6 (IQR 14.1-90) MMEs. Lower employment rates (p < 0.001), uninsured status (p = 0.016), and intravenous drug use (p = 0.006) were associated with preoperative opioid use. Preoperative opioid use was associated with increased venous thromboembolism (p = 0.001), acute kidney injury (p = 0.002), acute respiratory failure (p < 0.001), myocardial infarction (p = 0.002), delirium (p < 0.001), and infection (p < 0.001). Preoperative opioid use was an independent predictor of overall 90-day adverse events (OR 1.643, 95% CI 1.289-2.095; p < 0.001) and 90-day mortality (OR 1.690, 95% CI 1.254-2.277; p < 0.001). CONCLUSIONS: Preoperative opioid use was independently associated with 90-day postoperative adverse events and mortality. Opioid use increases vulnerability in craniotomy/craniectomy patients and necessitates close monitoring to improve outcomes.

A 316MP, 120FPS, High Dynamic Range CMOS Image Sensor for Next Generation Immersive Displays.

We present a 2D-stitched, 316MP, 120FPS, high dynamic range CMOS image sensor with 92 CML output ports operating at a cumulative date rate of 515 Gbit/s. The total die size is 9.92 cm × 8.31 cm and the chip is fabricated in a 65 nm, 4 metal BSI process with an overall power consumption of 23 W. A 4.3 µm dual-gain pixel has a high and low conversion gain full well of 6600e- and 41,000e-, respectively, with a total high gain temporal noise of 1.8e- achieving a composite dynamic range of 87 dB.

Impact of anemia on acute ischemic stroke outcomes: A systematic review of the literature.

INTRODUCTION: Anemia has been reported in nearly 40% of acute ischemic stroke (AIS) patients and is linked to significant morbidity and disability. The presence of anemia is associated with worse outcomes in AIS, specifically in the presence of large vessel occlusion (LVO). An optimal hemoglobin (Hb) target specific to this pathology has not yet been established. The goal of this review is to systematically review literature that observes the association that exists between AIS outcomes and hemoglobin (Hb) levels. METHODS: A systematic review was performed in accordance with guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to identify studies from 2008-2022. The following inclusion and exclusion criteria were used: studies of adult patients with AIS; must describe outcomes with regard to Hb levels in AIS (not limited to LVO); must be written in English. The clinical variables extracted included Length of Stay (LOS), modified rankin score (mRS), Hb levels, and mortality. RESULTS: A total of 1,154 studies were gathered, with 116 undergoing full text review. 31 studies were included in this review. The age of patients ranged from 61.4 to 77.8. The presence of anemia in AIS increased LOS by 1.7 days on average and these patients also have a 15.2% higher rate of mortality at one year, on average. DISCUSSION: This data suggests that the contemporary thresholds for treating anemia in AIS patients may be inadequate because anemia is strongly associated with poor outcomes (e.g., mRS>2 or mortality) and increased LOS in AIS patients. The current generalized Hb threshold for transfusion (7 g/dL) is also used in AIS patients, however, a more aggressive transfusion parameter should be further explored based on these findings. Further studies are required to confirm these findings and to determine if a more liberal RBCT threshold will result in clinical benefits.

Pretreatment findings on magnetic resonance imaging in primary central nervous system lymphoma may predict overall survival duration.

BACKGROUND: and purpose: Primary central nervous system lymphoma (PCNSL) lesions often show avid contrast enhancement on T1-weighted contrast-enhanced MRI sequences. However, several case reports and a clinical study have described PCNSL in patients with no contrast enhancement on MRI. We assessed whether overall survival (OS) time was related to any tumor characteristics (lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; and edema) on MRI in patients with PCNSL. MATERIALS AND METHODS: We retrospectively reviewed records (MRI features, pathology, and survival data) of all patients at our institution with PCNSL who had been seen from, 2007 through 2017, and had undergone pretreatment MRI. RESULTS: We identified 79 patients (42 men, 37 women) with a mean age at diagnosis of 61.7 ± 10.4 years. The mean OS duration was 44.6 ± 41.7 months. The most common pathological diagnosis (74 patients) was diffuse large B-cell lymphoma. No associations were found between OS time and lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; or edema. However, a sole patient with non-enhancing PCNSL on MRI was found to have low-grade disease, with prolonged survival (>83 months). Several other patients with leptomeningeal disease had a mean OS time of 80 months. Patients with hemorrhagic lesions had a mean OS of 25.5 months. CONCLUSIONS: The survival time for patients with PCNSL may be longer than previously thought, especially for patients with leptomeningeal seeding and lesions with hemorrhagic components Also, non-enhancing tumors may be less aggressive than enhancing tumors.

Localization matters in targeted protein degradation.

Many factors influence the efficiency of targeted protein degradation induced by proteolysis targeting chimeras (PROTACs). In this issue of Cell Chemical Biology,Simpson et al. (2022) highlight the impact of subcellular localization. Their study elucidates that the protein of interest exhibits different amenability to PROTAC-mediated degradation at different cellular compartments.

Effect of rapid EEG on anti-seizure medication usage

Objective: To study how early diagnoses from rapid EEG (rEEG) during the initial evaluation of patients with suspected non-convulsive seizures correlates with changes in anti-seizure medication (ASM) use. Methods: We performed a retrospective chart review of 100 consecutive adult patients at an academic medical center who underwent rEEG monitoring for suspected non-convulsive seizures. We collected information on the timing of ASM administration and categorized EEG diagnoses as seizures (SZ), highly epileptiform patterns (HEP), or normal or slow activity (NL/SL). We used a χ² test to determine whether the use of ASMs was significantly different between SZ/HEP and NL/SL cases. Results: Of 100 patients, SZ were found in 5%, HEP in 14%, and no epileptiform/ictal activity in 81%. Forty-six percent of patients had received ASM(s) before rEEG. While 84% of HEP/SZ cases were started or continued on ASMs, only 51% of NL/SL cases were started or continued on ASMs after rEEG (χ² [1, n=100] = 7.09, p=0.008). Thirty-seven patients had received sedation (i.e., propofol or dexmedetomidine) prior to rEEG. In 15 patients (13/30 NL/SL, 2/7 HEP/SZ), sedation was discontinued following rEEG. Significance: Our study demonstrates that seizures were rapidly ruled out with rEEG in 81% of patients while 19% of patients were rapidly identified as having seizures or being at higher risk for seizures. The rapid evaluation of patients correlated with a significant reduction in ASM treatment in NL/SL cases compared to HEP/SZ cases. Thus, early access to EEG information may lead to more informed and targeted management of patients suspected to have nonconvulsive seizures.

Utility of the novel guide catheter in mechanical thrombectomy for emergent large vessel occlusion stroke.

BACKGROUND: A number of large bore guide catheters are currently available for use in neuroendovascular surgery. This study represents a multi-institutional retrospective series of patients undergoing mechanical thrombectomy with the use of a TracStar Large Distal Platform (LDP) guide catheter and assessed its performance in vivo in 107 patients. OBJECTIVE: To review a multi-institutional initial experience with the TracStar LDP guide catheter during mechanical thrombectomy for emergent large vessel occlusion (ELVO). METHODS: A retrospective review was performed at two level one stroke centres to include all patients who underwent mechanical thrombectomy and had the TracStar LDP guide catheter used during the intervention. RESULTS: The TracStar LDP guide catheter was successfully used in 107 mechanical thrombectomies. In anterior circulation ELVO, the guide catheter advanced into the cavernous segment of the internal carotid artery in 62.6% (62/99) of cases. In posterior circulation cases, the guide catheter advanced to the basilar artery in 87.5% (7/8) of cases. A thrombolysis in cerebral infarction 2b or greater reperfusion was obtained in 90.7% (97/107). No complications occurred related to the TracStar LDP guide catheter. Three complications occurred with aspiration catheters including a small dissection that did not require further intervention and fracturing of the AXS Catalyst 6 catheter tip in two cases. No thromboembolic events occurred. CONCLUSIONS: The TracStar LDP large bore guide catheter is safe and effective at navigating the tortuous vascular anatomy often encountered during mechanical thrombectomy for stroke. The flexible distal and stiffer proximal components provide a good combination of navigability and support for use in neuroendovascular interventions.

Complications after 1002 endoscopic endonasal approach procedures at a single center: lessons learned, 2010-2018.

OBJECTIVE: The endoscopic endonasal approach (EEA) has evolved into a mainstay of skull base surgery over the last two decades, but publications examining the intraoperative and perioperative complications of this technique remain scarce. A prior landmark series of 800 patients reported complications during the first era of EEA (1998-2007), parallel to the development of many now-routine techniques and technologies. The authors examined a single-institution series of more than 1000 consecutive EEA neurosurgical procedures performed since 2010, to elucidate the safety and risk factors associated with surgical and postoperative complications in this modern era. METHODS: After obtaining institutional review board approval, the authors retrospectively reviewed intraoperative and postoperative complications and their outcomes in patients who underwent EEA between July 2010 and June 2018 at a single institution. RESULTS: The authors identified 1002 EEA operations that met the inclusion criteria. Pituitary adenoma was the most common pathology (n = 392 [39%]), followed by meningioma (n = 109 [11%]). No patients died intraoperatively. Two (0.2%) patients had an intraoperative carotid artery injury: 1 had no neurological sequelae, and 1 had permanent hemiplegia. Sixty-one (6.1%) cases of postoperative cerebrospinal fluid leak occurred, of which 45 occurred during the original surgical hospitalization. Transient postoperative sodium dysregulation was noted after 87 (8.7%) operations. Six (0.6%) patients were treated for meningitis, and 1 (0.1%) patient died of a fungal skull base infection. Three (0.3%) patients died of medical complications, thereby yielding a perioperative 90-day mortality rate of 0.4% (4 deaths). High-grade (Clavien-Dindo grade III-V) complications were identified after 103 (10%) EEA procedures, and multivariate analysis was performed to determine the associations between factors and these more serious complications. Extradural EEA was significantly associated with decreased rates of these high-grade complications (OR [95% CI] 0.323 [0.153-0.698], p = 0.0039), whereas meningioma pathology (OR [95% CI] 2.39 [1.30-4.40], p = 0.0053), expanded-approach intradural surgery (OR [95% CI] 2.54 [1.46-4.42], p = 0.0009), and chordoma pathology (OR [95% CI] 9.31 [3.87-22.4], p < 0.0001) were independently associated with significantly increased rates of high-grade complications. CONCLUSIONS: The authors have reported a large 1002-operation cohort of EEA procedures and associated complications. Modern EEA surgery for skull base pathologies has an acceptable safety profile with low morbidity and mortality rates. Nevertheless, significant intraoperative and postoperative complications were correlated with complex intradural procedures and meningioma and chordoma pathologies.

USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma.

Squamous cell carcinomas are therapeutically challenging tumor entities. Low response rates to radiotherapy and chemotherapy are commonly observed in squamous patients and, accordingly, the mortality rate is relatively high compared to other tumor entities. Recently, targeting USP28 has been emerged as a potential alternative to improve the therapeutic response and clinical outcomes of squamous patients. USP28 is a catalytically active deubiquitinase that governs a plethora of biological processes, including cellular proliferation, DNA damage repair, apoptosis and oncogenesis. In squamous cell carcinoma, USP28 is strongly expressed and stabilizes the essential squamous transcription factor ΔNp63, together with important oncogenic factors, such as NOTCH1, c-MYC and c-JUN. It is presumed that USP28 is an oncoprotein; however, recent data suggest that the deubiquitinase also has an antineoplastic effect regulating important tumor suppressor proteins, such as p53 and CHK2. In this review, we discuss: (1) The emerging role of USP28 in cancer. (2) The complexity and mutational landscape of squamous tumors. (3) The genetic alterations and cellular pathways that determine the function of USP28 in squamous cancer. (4) The development and current state of novel USP28 inhibitors.

Impact of Timing of Tocilizumab Use in Hospitalized Patients With SARS-CoV-2 Infection.

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to be a global challenge due to the lack of definitive treatment strategies. We sought to determine the efficacy of early administration of anti-interleukin 6 therapy in reducing hospital mortality and progression to mechanical ventilation. METHODS: This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of >88%. The Charlson comorbidity index was used as an objective assessment of the burden of comorbidities to predict 10-year mortality. The primary outcome of interest was hospital mortality. Secondary outcomes were progression to mechanical ventilation; the prevalence of venous thromboembolism and renal failure; and the change in C-reactive protein, D-dimer, and ferritin levels after tocilizumab administration. Propensity score matching by using a 1:2 protocol was used to match the tocilizumab and non-tocilizumab groups to minimize selection bias. The groups were matched on baseline demographic characteristics, including age, sex, and body mass index; Charlson comorbidity index score; laboratory markers, including ferritin, D-dimer, lactate dehydrogenase, and C-reactive protein values; and the maximum oxygen requirement at the time of tocilizumab administration. Mortality outcomes were evaluated based on the level of oxygen requirement and the day of hospitalization at the time of tocilizumab administration. RESULTS: The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P = .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator. CONCLUSIONS: Early use of anti-interleukin 6 therapy may be associated with improved hospital mortality and reduction in progression to more severe coronavirus disease 2019.

Comparison of Perioperative Outcomes and Parental Satisfaction Outcomes of Strip Craniectomy with Postoperative Helmet versus Spring-Mediated Remodeling in Sagittal Craniosynostosis.

INTRODUCTION: We sought to compare outcomes and parental satisfaction between 2 approaches for sagittal craniosynostosis: strip craniectomy with spring-mediated skull remodeling (SMSR) and strip craniectomy with postoperative helmet (SCH). METHODS: Perioperative and outcome data for SMSR or SCH patients between September 2010 and July 2019 were retrospectively reviewed. A telephone survey was administered to parents of children who underwent both procedures. RESULTS: A total of 62 children were treated for sagittal craniosynostosis by either SMSR (n = 45) or SCH (n = 17). The SCH group had a lower estimated blood loss (27 vs. 47.06 mL, p = 0.021) and age at surgery (13.0 vs. 19.8 weeks) than the SMSR group. Three patients underwent early springs removal due to trauma or dislodgement, all of whom converted to helmeting. Of the 62 children initially identified, 59 were determined to have an adequate follow-up time to assess long-term outcomes. The mean follow-up time was 30.1 months (n = 16) in the SCH group and 32.0 months in the SMSR group (n = 43, p = 0.39). Two patients in the SCH group and one in the SMSR group converted to open cranial vault reconstruction. Thirty parents agreed to respond to the satisfaction survey (8 SCH, 22 SMSR) based on a Likert scale of responses (0 being most dissatisfied possible, 4 most satisfied possible). Average satisfaction was 3.86/4.0 in the SCH group and 3.45/4.0 in the SMSR group. No parents in the SCH group would change to SMSR, while 3 of the 22 SMSR survey responders would have changed to SCH. CONCLUSIONS: Perioperative outcomes and average parental satisfaction were similar in both groups. Importance of helmet wear compliance and risk of spring dislodgement should be discussed with parents.

White Rann of Kachchh harbours distinct microbial diversity reflecting its unique biogeography.

The understanding of sub-surface soil microbial diversity is limited at both saline and hypersaline ecosystems, even though salinity is found to affect the microbial community in aqueous and terrestrial environment. In this study, a phylo-taxonomy analysis as well as the functional characteristics of microbial community of flat salt basin of White Rann of Kachchh (WR), Gujarat, India was performed along the natural salinity gradient. The high throughput sequencing approach has revealed the numerical abundance of bacteria relative to the archaea. Salinity, TOC, EC and sulphate concentration might be the primary driver of the community distribution along the transect at WR. The much anticipated effect of salinity gradient on the microbial composition surprisingly turned out to be more speculative, with little variance in the community composition along the spatial distance of WR. The metabolic pathways involved in energy metabolism (like carbon, nitrogen, sulphur) along with environmental adaptive genes (like osmotic and oxidative stress response, heat and cold shock genes clusters) were abundantly annotated from shot-gun metagenomic study. The carbonic anhydrase harbouring bacteria Bacillus sp. DM4CA1 was isolated from WR, having a catalytic ability for converting the gaseous carbon dioxide in presence of calcium carbonate into calcite at 25 % higher rate as compared to non-harbouring strains. The enzyme has a role in multiple alternative pathways in microbial metabolism. With the array of results obtained, the study could become the new reference for understanding the diversity structure and functional characteristics of the microbial community of terrestrial saline environment.

Minimized combinatorial CRISPR screens identify genetic interactions in autophagy.

Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs multiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed combinatorial CRISPR libraries. We demonstrate that the library distribution skew is the critical determinant of its required screening coverage. By circumventing iterative cloning of PCR-amplified oligonucleotides, 3Cs multiplexing facilitates the generation of combinatorial CRISPR libraries with low distribution skews. We show that combinatorial 3Cs libraries can be screened with minimal coverages, reducing associated efforts and costs at least 10-fold. We apply a 3Cs multiplexing library targeting 12,736 autophagy gene combinations with 247,032 paired gRNAs in viability and reporter-based enrichment screens. In the viability screen, we identify, among others, the synthetic lethal WDR45B-PIK3R4 and the proliferation-enhancing ATG7-KEAP1 genetic interactions. In the reporter-based screen, we identify over 1,570 essential genetic interactions for autophagy flux, including interactions among paralogous genes, namely ATG2A-ATG2B, GABARAP-MAP1LC3B and GABARAP-GABARAPL2. However, we only observe few genetic interactions within paralogous gene families of more than two members, indicating functional compensation between them. This work establishes 3Cs multiplexing as a platform for genetic interaction screens at scale.

Can an Imaging Marker of Consistency Predict Intraoperative Experience and Clinical Outcomes for Vestibular Schwannomas? A Retrospective Review.

Objective The main purpose of this article is to determine if vestibular schwannoma consistency as determined by tissue intensity on T2-weighted magnetic resonance imagings (MRIs) is predictive of intraoperative experience and postoperative clinical outcomes. Study Design Retrospective chart review. Setting Tertiary referral center. Patients Seventy-seven patients diagnosed with vestibular schwannomas who were treated with microsurgical resection. Intervention Diagnostic. Main Outcome Measures Intraoperative measures include totality of resection, surgical time and cranial nerve VII stimulation and postoperative measures include House-Brackmann grade and perioperative complications. Results Tumor consistency determined via tissue intensity on MRI was only found to correlate with surgical time, with a softer tumor being associated with a longer surgical time ( p < 0.0001). However, this was primarily driven by tumor volume with larger tumors being associated with longer surgical time based on multivariate analysis. None of the other intraoperative or postoperative measures considered were found to correlate with tumor consistency. Conclusions Tumor consistency determined by MRI is not predictive of intraoperative experience or postoperative outcomes in vestibular schwannomas. Tumor volume is the strongest driver of these outcome measures as opposed to tumor consistency.

Ultrasound's Impact on Preclinical Medical Student Neurology Unit Grades: Findings After 2 Years.

OBJECTIVES: Ultrasound is a valuable tool for anatomy education, but limited evidence exists for using ultrasound to teach neuroanatomy and neurophysiology. Previous work demonstrated a potential increase in medical knowledge in preclinical medical students participating in a neurology ultrasound workshop, however, without comparison to a control group. After 2 years, we assessed how a neurology ultrasound workshop affected the medical knowledge of participating preclinical medical students compared to a traditional curriculum control group. METHODS: This quasiexperimental study compared academic performance of ultrasound workshop participants to nonparticipant classmates. The primary outcome was the overall neurologic disorders unit total score. An analysis of covariance was conducted to test for statistically significant differences while controlling for the average quiz score. RESULTS: A total of 360 medical students were included in the study. The intervention group (n = 57) showed no significant difference in the total unit score (F = 3.206; P = .074), with averages for the control and experimental groups being 87.3% ± 5.0% and 88.4% ± 4.8%, respectively. Additionally, anatomy practical scores and written final examination scores were not significantly different between groups (F = 1.035; P = .310; F = 2.035; P = .155). CONCLUSIONS: Participation in a neurologic disorders ultrasound workshop did not appear to be correlated with improved curricular performance in our cohort. Further research should continue to assess ultrasound workshops in other organ systems to elucidate the relationship between learning ultrasound and the impact on medical school academic performance.

India Antimicrobial Stewardship and Resistance (INTEREST) 2018: A needs assessment survey.

Antimicrobial resistance is a major problem in India with limited understanding of whether this issue is related to systems, prescriber characteristics, patient characteristics, or diagnostic technologies. In our survey, most of the issues lie in the easy availability of antimicrobials and the lack of electronic storage of medical and microbiological records.

Anatomic feasibility of endoscopic endonasal intracranial aneurysm clipping: a systematic review of anatomical studies.

Clinical studies have suggested the endoscopic endonasal approach (EEA) for aneurysm clipping as a feasible way to treat select intracranial aneurysms. Among neurosurgery, there is not a consensus on the utility of EEA aneurysm clipping. This review aims to define the anatomic feasibility of EEA for aneurysm clipping. Two databases (PubMed, Cochrane) were searched for anatomical studies assessing EEA for intracranial aneurysm clipping. Literature review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quantitative anatomical studies were included. Eleven studies met inclusion criteria. Vascular exposure and clip placement on vessels of interest were possible, although only one study assessed these parameters with physical aneurysm models. Anterior circulation vessels, although accessible in over 90% of specimens, had low successful clipping rates in a small and large aneurysm models. Small and large model posterior circulation aneurysms were more readily clipped. Proximal and distal controls were readily attainable in posterior circulation aneurysms, but not anterior. This current literature review highlights the relevance of anatomical studies in assessing the feasibility of the EEA for clipping intracranial aneurysms. As such, anterior circulation aneurysms are poor candidates for EEA given difficulties in clip placement and obtaining proximal control and distal control in small and large aneurysms. While our results suggest that clipping of posterior circulation aneurysms is feasible from a technical stand of view, further clinical experience is required to assess its feasibility in terms of safety and efficacy, balancing the indications with endovascular treatment options.

A 51-Year-Old Man With Hoarseness of Voice.

CASE PRESENTATION: A 51-year-old nonsmoking man presented to his general practitioner with a primary complaint of 4 months of progressive hoarseness, and was subsequently referred to an otolaryngologist. He had no relevant medical or surgical history. He did not take any chronic medications or supplements. He was born in the Dominican Republic and moved to New York City when he was 36 years old. He worked in construction. In his spare time, he would return to his home country. The patient was a lifelong nonsmoker and reported no alcohol consumption. He denied shortness of breath, cough, sputum expectoration, fevers, chills, and night sweats.